The aortic valve regulates the flow of blood between the left ventricle and the aorta. Typically the aortic valve comprises three leaflets. The leaflets open during systole to define a valve orifice to allow blood to pass from the left ventricle to the aorta. The valve orifice is the opening defined by the leaflets at the narrowest portion of an open aortic valve during systole. The leaflets close during diastole to prevent blood flow from the aorta back to the left ventricle. Aortic stenosis generally refers to an aortic valve wherein one or more leaflets become thickened and/or deformed due to calcification or other disease modality. The diseased leaflets may not open fully causing a restriction of blood flow and a higher pressure gradient across the smaller-than-normal valve orifice. The higher the pressure gradient across the valve orifice generally corresponds to a higher degree of aortic stenosis and therefore an indicator of a greater level of disease.
Table 1 shows how the typical mean pressure gradient varies with the severity of aortic stenosis.
TABLE 1Severity of Aortic StenosisDegree ofMean pressureValve orificeaortic stenosisgradient (mmHg)area (cm2)Mild<25>1.5Moderate25-401.0-1.5Severe>40<1.0Critical>70<0.6From: http://en.wikipedia.org/wiki/Aortic_valve_stenosis
Quantifying the degree of aortic stenosis is critical to proper medical treatment of the patient. Mild aortic stenosis may be left untreated but monitored subject to the significance of any clinical symptoms. Moderate aortic stenosis may be treated with cholesterol lowering medications or other Pharmaceuticals. Severe to critical aortic stenosis may be surgically treated using methods such as catheter-based interventions and valve replacement but with the associated risks of surgical treatment.
The principle imaging modality for quantifying aortic stenosis is transthoracic echocardiography. The technique is noninvasive by using ultrasound to make images of the heart and to measure the velocity of blood flow at the valve orifice using Doppler data. The modified Bernoulli equation is commonly used to calculate the pressure gradient across a stenotic valve orifice where velocity at the valve orifice is known. The simplified general mathematical relationship is:Pressure Gradient (mm Hg)=4*Velocity2  (EQ. 1)
Similarly, the transvalvular peak pressure gradient (PPG) at the valve orifice is estimated by measuring the peak velocity (Vp) of blood as it passes through the narrowest part of the valve orifice. The mathematical relationship is:PPG (mm Hg)=4*Vp2  (EQ. 2)
In healthy individuals, Vp is typically about 1 m/s. In patients with mild aortic stenosis Vp is 2-3 m/sec. Peak velocities of 3-4 m/s are often found in patients with moderate aortic stenosis. Patients with severe aortic stenosis generally have peak velocities greater than 4 m/s.
Physicians sometimes also use the mean pressure gradient to determine the severity of aortic stenosis. The mean pressure gradient can be estimated by summing the instantaneous pressures during systole and dividing by the systolic ejection time. The instantaneous pressures are calculated from the instantaneous blood velocities at the valve orifice and the modified Bernoulli equation. Alternatively, the mean pressure gradient can be estimated by the following formula:
                              mean          ⁢                                          ⁢          Δ          ⁢                                          ⁢                      P            ⁡                          (              mmHg              )                                      =                  2.4          ×                                    v              ⁡                              (                                  m                  s                                )                                      max            2                                              (                  EQ          .                                          ⁢          3                )            
Table 1 also lists a third parameter that physicians use to assess the severity of aortic stenosis, namely the aortic valve area (AVA), also referred herein as valve orifice area. Valve orifice area is defined as the area of the valve orifice on a planar slice through the narrowest portion of an open aortic valve during systole.
In echocardiography it is theoretically possible to measure the AVA directly by using planimetry on the valve orifice during systole when the aortic valve is open to the maximum extent. However, in most patients with aortic stenosis, the aortic valve is heavily calcified. Calcification blocks the ultrasound beam and prevents imaging so that it is usually impossible to accurately planimeter the valve orifice.
In practice, the determination of orifice area by echocardiography is usually calculated using the continuity equation. The basic premise of the continuity equation is that the volumetric flow rate, also referred herein as “flow rate”, proximal to the area of aortic stenosis, such as in the left ventricular outflow tract (LVOT), must equal the volumetric flow rate at the valve orifice, assuming that blood is essentially an incompressible fluid. Commonly, the AVA is calculated using the following equation:AVA=(AreaLVOT)*(VTILVOT/VTIAV)  (EQ. 4)
In equation 4, the area of the LVOT is often expressed in cm2. The area of the LVOT is determined by measuring the LVOT diameter (DLVOT) and assuming that it is a circle (AreaLVOT=3.14*DLVOT2/4). The VTI (velocity time integral) is the integral of the velocity-time curve obtained from the ultrasound-derived Doppler signal of the volumetric flow rate of the blood in the respective locations.
The normal aortic valve area and the significance of aortic valve stenosis depend in part on the size of the patient. Some investigators will divide the aortic valve area by the body surface area of the patient to determine the aortic valve area index (AVAI). Body surface area is calculated from a formula that uses the height and weight of the person as inputs. A scale of degree of severity based on the aortic valve area index (AVAI) has been used by some in the art.
The use of transthoracic echocardiography for quantifying aortic stenosis in accordance with the three methods discussed above introduces errors and assumptions that may not provide accurate determination of the pressure gradient across a stenotic aortic valve. These errors and assumptions include, but are not limited to, inaccurate average or peak velocity measurements at the valve orifice and inaccurate body surface assumptions.
MRI may be used in an analogous manner to echocardiography. Namely, velocities of blood may be imaged by MRI and used to calculate a peak pressure gradient using the modified Bernoulli equation, and velocities may be used to calculate the aortic valve area using the continuity equation. However, MRI has different strengths and weaknesses than echocardiography. While MRI can measure velocities with phase-contrast techniques, performing this method often adds to the total cardiac MRI examination time. In addition, there are a number of sources of errors to the velocity measurement. Sources of error include turbulent flow, partial volume averaging, flow not perpendicular to the imaging slice, and baseline offset errors due to eddy currents.
For MRI to make the same measurements in an analogous manner to echocardiography, the user typically will acquire a series of contiguous parallel imaging planes starting at the left ventricular outflow tract and extending through the aortic valve leaflets. The slices are oriented substantially perpendicular to the direction of blood flow, A phase-contrast imaging sequence is used to capture velocity data throughout the cardiac cycle. After the images are acquired, the user will typically select the phase of the cardiac cycle where blood flow is maximal. Using a region of interest, the user will determine the blood velocity within the left ventricular outflow tract (VpLvor). The user will then determine the peak velocity (VpAv) of blood flow at the valve orifice. According to the simplified Bernoulli equation, the peak pressure gradient will be 4*Vp2. According to the continuity equation, the aortic valve area will be AreaLvoi*(VpLvoiNpAv).
Similar to transthoracic echocardiography, the use of MRI to provide velocity data for quantifying aortic stenosis in accordance with the method discussed above introduces errors and assumptions that may not provide accurate determination of the pressure gradient across a stenotic aortic valve.
For patients in whom echocardiography is unable to unambiguously determine the severity of the aortic stenosis, and for those patients where the clinical symptoms do not correlate with the echocardiographic findings, cardiac catheterization is often used to determine the severity of the aortic stenosis. In this procedure a catheter is introduced into a peripheral artery and advanced retrograde through the aorta until the tip traverses the aortic valve. With this procedure, a physician can directly measure the pressure gradient across the valve orifice. Using a catheter based thermodilution technique, cardiac output can also be estimated. The aortic valve area may be estimated using the Gorlin equation:
                              Aortic          ⁢                                          ⁢          Valve          ⁢                                          ⁢          Area          ⁢                                          ⁢                      (                          cm              2                        )                          =                              Cardiac            ⁢                                                  ⁢                          Output              ⁡                              (                                  ml                  min                                )                                                          Heart            ⁢                                                  ⁢                          Rate              ⁡                              (                                  beats                  min                                )                                      ×            Systolic            ⁢                                                  ⁢            Ejection            ⁢                                                  ⁢                          Period              ⁡                              (                s                )                                      ×                                                  ⁢                                                  ⁢            44.3            ×                                          mean                ⁢                                                                  ⁢                Gradient                ⁢                                                                  ⁢                                  (                  mmHg                  )                                                                                        (                  EQ          .                                          ⁢          5                )                            or the even simpler Haaki equation:        
                              Valve          ⁢                                          ⁢          Area          ⁢                                          ⁢                      (                          cm              2                        )                          =                              Cardiac            ⁢                                                  ⁢            Output            ⁢                                                  ⁢                          (                              liter                min                            )                                                          mean              ⁢                                                          ⁢              Gradient              ⁢                                                          ⁢                              (                mmHg                )                                                                        (                  EQ          .                                          ⁢          6                )            
Although it is considered the “gold standard” test, catheterization is an invasive procedure and carries potentially serious risks to the patient such as infection, aortic dissection (a tear within the wall of the aorta), and stroke. Cardiac catheterization introduces its own errors and assumptions that may not provide accurate determination of the pressure gradient across a stenotic aortic valve.
An inaccurate pressure gradient determination may directly impact the treatment plan for the patient. If the pressure gradient is under predicted, a lower degree of severity of disease will be predicted, resulting in, such as, but not limited to, a delay in or less aggressive treatment intervention possibility leading to continued or worsening patient morbidity. If the pressure gradient is over predicted, a higher degree of severity of disease will be predicted, resulting in, such as, but not limited to, an over aggressive treatment with its underlying increase of risks to the patient and increased costs that may not be necessary.
It would therefore be desirable to provide non-invasive apparatus and methods for more accurately determining the pressure gradient across a cardiovascular orifice, such as, but not limited to, a stenotic aortic valve.